title: A role of p38 mitogen-activated protein kinase in adenosine A₁ receptor-mediated synaptic depotentiation in area CA1 of the rat hippocampus.
abstract: BACKGROUND
  Although long-term potentiation (LTP) of synaptic strength is very persistent, current studies have provided evidence that various manipulations or pharmacological treatment when applied shortly after LTP induction can reverse it. This kind of reversal of synaptic strength is termed as depotentiation and may have a function to increase the flexibility and storage capacity of neuronal networks. Our previous studies have demonstrated that an increase in extracellular levels of adenosine and subsequent activation of adenosine A₁ receptors are important for the induction of depotentiation; however, the signaling downstream of adenosine A₁ receptors to mediate depotentiation induction remains elusive.
  
  
  RESULTS
  We confirm that depotentiation induced by low-frequency stimulation (LFS) (2 Hz, 10 min, 1200 pulses) was dependent on adenosine A₁ receptor activation, because it was mimicked by bath-applied adenosine A₁ receptor agonist N⁶-cyclopentyladenosine (CPA) and was inhibited by the selective adenosine A₁ receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Pretreatment of the hippocampal slices with the selective p38 mitogen-activated protein kinase (MAPK) inhibitors, 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl]-5-(4-pyrudyl)-1H-imidazole (SB203580) or trans-1-(4-hydroxycyclohexyl)-4-(fluorophenyl)-5-(2-methoxypyrimidin-4-yl)imidazole (SB239063), prevented the induction of depotentiation by LFS and CPA. In agreement with electrophysiological observation, both LFS- and CPA-induced depotentiation are associated with an increase in p38 MAPK activation, which are blocked by DPCPX or SB203580 application.
  
  
  CONCLUSIONS
  These results suggest that activation of adenosine A₁ receptor and in turn triggering p38 MAPK signaling may contribute to the LFS-induced depotentiation at hippocampal CA1 synapses.
authors.affiliation: Department of Pharmacology, National Cheng Kung University, Tainan City, Taiwan. alice217@ms35.url.com.tw
authors.forename: Ying-Ching
authors.initials: YC
authors.lastname: Liang
authors.forename: Chiung-Chun
authors.initials: CC
authors.lastname: Huang
authors.forename: Kuei-Sen
authors.initials: KS
authors.lastname: Hsu
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*; D004558:Electric Stimulation; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D043682:Receptor, Adenosine A1; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580